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Kleine-Levin Syndrome

Syndrome Kleine Levin

Kleine-Levin syndrome is rare sleep disorder characterized by episodic hypersomnia, cognitive dysfunction, psychiatric and behavioral disturbances.


Presentation

Episodic hypersomnia, hyperphagia, and hypersexual behavior has been referred to as the classical symptom triad but is presented by only half of KLS patients. In the majority of patients, cognitive dysfunction, hallucinations, and déjà vu-like experiences accompany hypersomnia [4].

In detail, the following symptoms have been related to the disease [5]:

During early stages of the disease, KLS episodes may be experienced several times a year, but frequency declines over time. Similarly, the severity of symptoms gradually decreases with disease progression. A single episode typically lasts about ten days [3], but may also extend over more than a month [7]. Between episodes, affected individuals may present unaltered sleep, eating and sexual patterns, but a trend towards fatigue and higher incidence rates of anxiety and depression has been registered [8].

Patients may or may not be able to recall a KLS episode.

Weight Gain
  • If you experience increased hunger and overeat during episodes, you may be more likely to experience weight gain. Talk to your doctor about how to best identify an approaching episode. Tiredness and sleepiness caused by KLS can occur suddenly.[healthline.com]
  • Overeating and binge eating are found with both syndromes. 20 to 30 kilograms in weight gain associated with the onset of narcolepsy is not unusual, and it is found that later on, 25 percent of patients overeat, especially late in the evening or at night[nodss.org.au]
  • You may feel an overwhelming urge to eat anything available, often resulting in weight gain. Disorientation . People report that they feel vague, dream-like, confused or disorientated when awake.[nosleeplessnights.com]
  • A 9-year-old boy presented with complaints of excessive duration of sleep, increased appetite, weight gain, excessive daytime sleepiness, loss of interest in sports activities, irritability and snoring since 1.5 years after he was shifted to a residential[doi.org]
Constitutional Symptom
  • Constitutive symptoms described in KLS patients include fever (68%), hot flashes (24%) and sweating (46%), migraine-like headaches (48%), photophobia (59%) and nausea (18%).[symptoma.com]
Overeating
  • Seven subjects with Kleine-Levin Syndrome accumulated over time had systematic SPECT studies during (n 5) and out (n 7) of the symptomatic period.[ncbi.nlm.nih.gov]
  • A single episode typically lasts about ten days, but may also extend over more than a month.[symptoma.com]
  • This study reports a male adolescent with KLS who received several courses of drug therapy, providing a chance to compare differential drug effects over time.[ncbi.nlm.nih.gov]
  • Just over half of patients have hyperphagia, are hypersexual (mainly boys), or have depressed mood (mainly girls), and 30% become anxious, delusional, and have hallucinations.[ncbi.nlm.nih.gov]
  • Over the past decade, numerous neuroimaging studies have been performed to characterize the pathophysiology and various clinical features of narcolepsy.[ncbi.nlm.nih.gov]
Increased Appetite
  • Kleine-Levin syndrome is a rare self-limited disorder which usually affects adolescent males and is characterized by episodic hypersomnia, increased appetite, and behavioral/psychiatric disturbances. Individuals are normal between the attacks.[ncbi.nlm.nih.gov]
  • The article reported a case of 10-year-old boy with a two-week history of altered sensorium, irrelevant talks, markedly increasing appetite and tendency to sleep most of the times.[ncbi.nlm.nih.gov]
  • At the age of 14, he presented with complaints of the excessive duration of sleep, increased appetite, excessive daytime sleepiness, loss of interest in social activities during attendance of high school and hallucinations.[ncbi.nlm.nih.gov]
  • Symptoms of Kleine-Levin syndrome include excessive daytime sleepiness and sleeping for long stretches (patients sometimes wake only to eat and use the bathroom), sometimes accompanied by increased appetite and hypersexuality, for a period of 2 to 31[tuck.com]
  • Episodes can also trigger other symptoms, such as: hallucinations disorientation irritability childish behavior increased appetite excessive sex drive This may result from reduced blood flow to parts of the brain during an episode.[healthline.com]
Loss of Appetite
  • Eating disorders comprise hyperphagia (66%) and excessive drinking (16%), but a loss of appetite (34%) may also be claimed. An excess sexual drive (59%) is much more common than decreased sexuality (6%) and is more often observed in male patients.[symptoma.com]
Acne Vulgaris
  • The synthetic retinoid isotretinoin is an effective treatment option for severe forms of acne vulgaris. However, several reports indicate that some patients experience altered central nervous system functions in association with treatment.[ncbi.nlm.nih.gov]
Confusion
  • The episodic disorder was characterised by excessive sleep, voracious appetite, irritability, confusion and electro-encephalographic changes. Remission was spontaneous.[ncbi.nlm.nih.gov]
  • This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants.[ncbi.nlm.nih.gov]
  • During episodes, patients suddenly present hypersomnia (with sleep lasting 15-21 h/d), cognitive impairment (major apathy, confusion, slowness, amnesia), and a specific feeling of derealization (dreamy state, altered perception).[ncbi.nlm.nih.gov]
  • Depression, confusion, and thought disorders are frequently associated with the critical symptomatology, and they may suggest other psychiatric diagnoses (schizophrenia, mood disorder, conversion disorder) or a substance abuse.[ncbi.nlm.nih.gov]
  • It is characterized by episodes lasting from 1 to several weeks, and comprises neurological (hypersomnia, confusion, slowness, amnesia) and neuropsychiatric symptoms (derealization and apathy).[ncbi.nlm.nih.gov]
Irritability
  • The episodic disorder was characterised by excessive sleep, voracious appetite, irritability, confusion and electro-encephalographic changes. Remission was spontaneous.[ncbi.nlm.nih.gov]
  • Psychiatric manifestations are common to both and include irritability, depression, apathy, inattention and poor concentration. Both disorders are diagnosed clinically and no specific laboratory investigation is available to confirm the diagnosis.[ncbi.nlm.nih.gov]
  • Stimulants marginally address sleepiness, but may increase irritability and do not improve cognitive and behavioral disturbances. Modafinil may shorten the symptomatic period but not the recurrence rate.[ncbi.nlm.nih.gov]
  • Abstract Six days after the onset of influenza B symptoms, a 14-year-old Japanese boy presented with encephalopathy-like symptoms, somnolence, irritability, and childishness, which we first considered was an atypical type of influenza-associated encephalopathy[doi.org]
  • Six days after the onset of influenza B symptoms, a 14-year-old Japanese boy presented with encephalopathy-like symptoms, somnolence, irritability, and childishness, which we first considered was an atypical type of influenza-associated encephalopathy[ncbi.nlm.nih.gov]
Amnesia
  • During episodes, patients suddenly present hypersomnia (with sleep lasting 15-21 h/d), cognitive impairment (major apathy, confusion, slowness, amnesia), and a specific feeling of derealization (dreamy state, altered perception).[ncbi.nlm.nih.gov]
  • It is characterized by episodes lasting from 1 to several weeks, and comprises neurological (hypersomnia, confusion, slowness, amnesia) and neuropsychiatric symptoms (derealization and apathy).[ncbi.nlm.nih.gov]
  • During episodes, patients with prolonged episodes had shorter sleep time, higher levels of anxiety, increased agitation, and more feelings of disembodiment and amnesia.[ncbi.nlm.nih.gov]
  • During episodes, all patients have hypersomnia (with sleep periods lasting 15-21 hours per day), cognitive impairment (apathy, confusion, slowness and amnesia) and a specific feeling of derealization (a dream-like state with altered perception).[orpha.net]
  • On recovery, total or partial loss of memory (amnesia) of what has happened is usual. There may be a short period of depression, or sometimes euphoria and sleeplessness.[southerncross.co.nz]
Lethargy
  • When awake, affected individuals may exhibit irritability, lack of energy (lethargy), and/or lack of emotions (apathy). They may also appear confused (disoriented) and experience hallucinations When present, symptoms may persist for days to weeks.[psychnet-uk.com]
  • Characteristic symptoms may include: Childlike or “spacey” demeanour Confusion and disorientation Lethargy and fatigue Lack of emotions and focus Photosensitivity and phonosensitivity Compulsive hyperphagia (food cravings) Hyper-sexuality The symptoms[news-medical.net]
  • When awake the patient experiences confusion, disorientation, complete lack of energy (lethargy), and lack of emotions (apathy). Most patients report that everything seems out of focus, and that they are hypersensitive to noise and light.[klsfoundation.org]
  • During wakefulness patients experience symptoms including disorientation, confusion, hallucinations, irritability, lethargy and apathy. They are not able to care for themselves or attend school or school.[globalgenes.org]
Seizure
  • Hence, in view of seizure disorder and lack of response, neurologist's consultation was sought, who opined to start antiepileptic medication.[ijpm.info]
  • Brain researchers believe such seizures can occur when the part of the brain that processes emotions associated with a certain type of music overlap with areas of the brain that trigger seizures.[abcnews.go.com]
  • She was also seen by doctors, who diagnosed her with partial complex seizures, one of the neurological conditions that has characteristics that mimic but don't fully match KLS.[cbc.ca]

Workup

According to The International Classification of Sleep Disorders [9], KLS falls into the categories "hypersomnias of central origin" and "recurrent hypersomnia." Diagnostic criteria are defined as follows:

  • A minimum of two episodes of hypersomnia each lasting more than two days and less than five weeks.
  • A month to one and a half years lie between single episodes.
  • Episodes are further characterized by at least one of the following symptoms: eating disorder, disinhibited behavior, cognitive impairment, altered perception.
  • Between episodes, consciousness, cognitive function, mood, and behavior remain unaltered.
  • Symptoms cannot be explained by other pathologies, e.g., epilepsy, narcolepsy, bipolar disorder, or medication.

Thus, thorough anamnesis, general and neurological examinations are the mainstays of KLS diagnosis. Additional measures may be carried out to rule out psychiatric disorders.

In this context, polysomnography [10], brain imaging, laboratory analyses of blood or cerebrospinal fluid, and neuropsychological tests may be performed [4].

Treatment

  • On the basis of this knowledge, practical information is offered to help clinicians about how to investigate a case of KLS, and what are the possible treatment modalities available currently for the treatment during an episode and interepisodic period[ncbi.nlm.nih.gov]
  • The synthetic retinoid isotretinoin is an effective treatment option for severe forms of acne vulgaris. However, several reports indicate that some patients experience altered central nervous system functions in association with treatment.[ncbi.nlm.nih.gov]
  • This provides scope for offering established and effective migraine treatment options to patients who with a potential misdiagnosis of Kleine-Levin syndrome, providing scope for offering established and effective migraine treatment to some patients originally[ncbi.nlm.nih.gov]
  • Lithium therapy stops episodes in 37% patients (vs. 3.4% if no treatment is given) and reduces the frequency/duration of episodes in 46% of other patients. The treatment is usually given to patients with frequent, prolonged or very severe episodes.[orpha.net]
  • AUTHORS' CONCLUSIONS: Therapeutic trials of pharmacological treatment for Kleine-Levin Syndrome, with a double-blind, placebo-controlled design are needed.[ncbi.nlm.nih.gov]

Prognosis

  • There is no specific therapy, but the disease is self-limited and with good prognosis.[ncbi.nlm.nih.gov]
  • The prognosis is generally benign, with normal cognitive and social functions after the episodes.[ncbi.nlm.nih.gov]
  • Prognosis The prognosis is generally good, with most patients presenting less frequent and less severe episodes with advancing age and disappearance of the syndrome around 30-35 y old.[orpha.net]
  • The prognosis, however, is felt to be overall favorable, as episodes become progressively milder and less frequent before resolving entirely in most patients. Copyright 2016. Published by Elsevier Ltd.[ncbi.nlm.nih.gov]
  • […] for the triad of hypersomnia, excessive eating and "often abnormal behavior" which they have observed in 11 adolescent boys, the number of patients recognized with this rare syndrome expanded, the spectrum of the clinical presentation, disease course, prognosis[ncbi.nlm.nih.gov]

Etiology

  • In this study, PubMed was searched and appropriate articles were reviewed to highlight etiology, clinical features, and management of KLS.[ncbi.nlm.nih.gov]
  • Kleine-Levin syndrome (KLS) is a rare sleep disorder of unknown etiology which diagnosis is clinical and diagnostic workup is mainly to exclude other similar conditions.[ncbi.nlm.nih.gov]
  • Kleine-Levin syndrome is a rare sleep disorder of unknown etiology. It is characterized by intermittent periods of excessive sleepiness, cognitive disturbances and behavioral abnormalities.[ncbi.nlm.nih.gov]
  • Kleine-Levin syndrome: Etiology, diagnosis, and treatment.[doi.org]
  • BACKGROUND: Kleine-Levin syndrome (KLS) is a rare disorder of unknown etiology. Pathophysiologic hypotheses include a hypothalamic dysfunction and abnormalities in the central serotonin and dopamine metabolism.[ncbi.nlm.nih.gov]

Epidemiology

  • Summary Epidemiology It affects around 1/500 000 individuals. Patients are mostly male (68-78% of cases) and adolescents (81% of patients), with a mean age of onset of 15 years (range 4-82 years).[orpha.net]
  • This rare disorder has been studied more closely in the last few years with abundant epidemiologic data assembled through literature and worldwide case reviews.[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Kleine-Levin syndrome (KLS) is a rare disorder whose pathophysiological mechanisms remain unknown.[ncbi.nlm.nih.gov]
  • Comprehensive research into the etiology, pathophysiology, investigation, and treatments are required to aid the development of disease-specific targeted therapies.[ncbi.nlm.nih.gov]
  • The differential diagnosis of this syndrome is discussed and a review of the literature is presented including evidence and hypotheses regarding its pathophysiology.[ncbi.nlm.nih.gov]
  • Over the past decade, numerous neuroimaging studies have been performed to characterize the pathophysiology and various clinical features of narcolepsy.[ncbi.nlm.nih.gov]
  • The etiology, pathophysiology, and optimal management of KLS remain uncertain.[ncbi.nlm.nih.gov]

Prevention

  • Here, we report a case of recurrent hypersomnia in which gabapentin was effective for the prevention of attacks.[ncbi.nlm.nih.gov]
  • The severity of hypersomnia prevented her from attending school activities. Outside the hypersomnia periods, she was asymptomatic.[ncbi.nlm.nih.gov]
  • It concludes that the cause remains unknown and no treatment is effective in preventing recurrence, although modafinil may reduce duration of symptomatic episode.[ncbi.nlm.nih.gov]
  • Prevention of Sleeping Beauty Syndrome or Kleine-Levin Syndrome Lithium is the only element or drug that has a preventive effect on Sleeping Beauty Syndrome or Kleine-Levin Syndrome.[epainassist.com]
  • Because of similarities between Kleine-Levin syndrome and certain mood disorders, lithium and carbamazepine may be prescribed and, in some cases, have been shown to prevent further episodes.[ninds.nih.gov]

Summary

Kleine-Levin syndrome (KLS) is a rare disease with as-of-yet unknown etiology. Affected individuals suffer from episodic hypersomnia, cognitive impairment, and an altered mental state. It has been speculated that these symptoms indicate hypothalamic lesions, although scientific evidence regarding this hypothesis is scarce. Disease onset has been related to encephalitis [1], though, single episodes may be triggered by infection, head trauma, alcohol or drug abuse. Familial KLS has also been described [2].

To date, symptomatic treatment is not available. Spontaneous remission is likely, though, particularly in patients who experience first episodes of hypersomnia during adolescence. However, years may pass until resolution occurs [3].

References

Article

  1. Fenzi F, Simonati A, Crosato F, Ghersini L, Rizzuto N. Clinical features of Kleine-Levin syndrome with localized encephalitis. Neuropediatrics. 1993;24(5):292-295.
  2. Nguyen QT, Groos E, Leclair-Visonneau L, et al. Familial Kleine-Levin Syndrome: A Specific Entity? Sleep. 2016;39(8):1535-1542.
  3. Arnulf I, Zeitzer JM, File J, Farber N, Mignot E. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain. 2005;128(Pt 12):2763-2776.
  4. Miglis MG, Guilleminault C. Kleine-Levin syndrome: a review. Nat Sci Sleep. 2014;6:19-26.
  5. Arnulf I, Lin L, Gadoth N, et al. Kleine-Levin syndrome: a systematic study of 108 patients. Ann Neurol. 2008;63(4):482-493.
  6. Arnulf I, Rico TJ, Mignot E. Diagnosis, disease course, and management of patients with Kleine-Levin syndrome. Lancet Neurol. 2012;11(10):918-928.
  7. Miglis MG, Guilleminault C. Kleine-Levin Syndrome. Curr Neurol Neurosci Rep. 2016;16(6):60.
  8. Millichap JG. Differential Diagnosis of Kleine-Levin Syndrome. Pediatr Neurol Briefs. 2015;29(3):24.
  9. American Academy of Sleep Medicine. International classification of sleep disorders: diagnostic and coding manual. 3rd ed. Westchester, USA: American Academy of Sleep Medicine;2014.
  10. Huang YS, Lin YH, Guilleminault C. Polysomnography in Kleine-Levin syndrome. Neurology. 2008;70(10):795-801.

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Last updated: 2019-07-11 21:01